Knowledge gaps in psychedelic medicalisation: Preclinical and neuroimaging mechanisms

Classical psychedelic drugs, e.g., psilocybin and LSD, stimulate the serotonin 2A receptor (5-HT2AR) and have recently been intensely investigated for their clinical effects in various brain disorders. At the ECNP "New Frontiers meeting" in March 2023, scientific experts in psychedelics met to identify key knowledge gaps in the mechanism of action of psychedelics as investigated using preclinical models and clinical neuroimaging. Key themes included the development of appropriate behavioural models for measuring acute and persisting effects, dose optimisation, molecular mechanisms of action, sex differences, and the acute and persisting effects of psychedelics on neurotransmitter release and functional brain activity.